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1.
Proc Natl Acad Sci U S A ; 118(31)2021 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-34282032

RESUMO

Changes in the distribution and abundance of invasive species can have far-reaching ecological consequences. Programs to control invaders are common but gauging the effectiveness of such programs using carefully controlled, large-scale field experiments is rare, especially at higher trophic levels. Experimental manipulations coupled with long-term demographic monitoring can reveal the mechanistic underpinnings of interspecific competition among apex predators and suggest mitigation options for invasive species. We used a large-scale before-after control-impact removal experiment to investigate the effects of an invasive competitor, the barred owl (Strix varia), on the population dynamics of an iconic old-forest native species, the northern spotted owl (Strix occidentalis caurina). Removal of barred owls had a strong, positive effect on survival of sympatric spotted owls and a weaker but positive effect on spotted owl dispersal and recruitment. After removals, the estimated mean annual rate of population change for spotted owls stabilized in areas with removals (0.2% decline per year), but continued to decline sharply in areas without removals (12.1% decline per year). The results demonstrated that the most substantial changes in population dynamics of northern spotted owls over the past two decades were associated with the invasion, population expansion, and subsequent removal of barred owls. Our study provides experimental evidence of the demographic consequences of competitive release, where a threatened avian predator was freed from restrictions imposed on its population dynamics with the removal of a competitively dominant invasive species.


Assuntos
Distribuição Animal , Espécies Introduzidas , Estrigiformes/fisiologia , Animais , Ecossistema , Noroeste dos Estados Unidos , Dinâmica Populacional
2.
Biometrics ; 75(3): 799-809, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31004437

RESUMO

Over the past decade, there has been much methodological development for the estimation of abundance and related demographic parameters using mark-resight data. Often viewed as a less-invasive and less-expensive alternative to conventional mark recapture, mark-resight methods jointly model marked individual encounters and counts of unmarked individuals, and recent extensions accommodate common challenges associated with imperfect detection. When these challenges include both individual detection heterogeneity and an unknown marked sample size, we demonstrate several deficiencies associated with the most widely used mark-resight models currently implemented in the popular capture-recapture freeware Program MARK. We propose a composite likelihood solution based on a zero-inflated Poisson log-normal model and find the performance of this new estimator to be superior in terms of bias and confidence interval coverage. Under Pollock's robust design, we also extend the models to accommodate individual-level random effects across sampling occasions as a potentially more realistic alternative to models that assume independence. As a motivating example, we revisit a previous analysis of mark-resight data for the New Zealand Robin (Petroica australis) and compare inferences from the proposed estimators. For the all-too-common situation where encounter rates are low, individual detection heterogeneity is non-negligible, and the number of marked individuals is unknown, we recommend practitioners use the zero-inflated Poisson log-normal mark-resight estimator as now implemented in Program MARK.


Assuntos
Demografia/estatística & dados numéricos , Modelos Biológicos , Modelos Estatísticos , Animais , Densidade Demográfica , Tamanho da Amostra , Aves Canoras
3.
Blood Cells Mol Dis ; 63: 1-8, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27888688

RESUMO

An oral therapeutic which reduces duration of cytopenias and is active following accidental radiation exposures is an unmet need in radiation countermeasures. Alpha methylhydrocinnamate (ST7) prolongs STAT-5 phosphorylation, reduces growth-factor dependency of multi-lineage cell lines, and stimulates erythropoiesis. Here, ST7 and its isomers were studied for their effects on myeloid progenitors and hematopoietic stem cells (HSCs) following radiation, in nonhuman primates, and murine irradiation models. Addition of ST7 or ST7-S increased CFU-GM production by 1.7-fold (p<0.001), reduced neutrophil apoptosis comparable to G-CSF, and enhanced HSC survival post-radiation by 2-fold, (p=0.028). ST7 and ST7-S administered in normal baboons increased ANC and platelet counts by 50-400%. In sub-lethally-irradiated mice, ANC nadir remained >200/mm3 and neutropenia recovered in 6days with ST7 treatment and 18days in controls (p<0.05). In lethally-irradiated mice, marrow pathology at 15days was hypocellular (10% cellularity) in controls, but normal (55-75% cellularity) with complete neutrophil maturation with ST7-S treatment. Following lethal irradiation, ST7, given orally for 4days, reduced mortality, with 30% survival in ST7-animals vs 8% in controls, (p<0.05). Collectively, the studies indicate that ST7 and ST7-S enhance myeloid recovery post-radiation and merit further evaluation to accelerate hematologic recovery in conditions of radiation-related and other marrow hypoplasias.


Assuntos
Células Mieloides/efeitos dos fármacos , Neutrófilos/efeitos dos fármacos , Fenilpropionatos/uso terapêutico , Recuperação de Função Fisiológica/efeitos dos fármacos , Irradiação Corporal Total/efeitos adversos , Animais , Células-Tronco Hematopoéticas/efeitos dos fármacos , Células-Tronco Hematopoéticas/efeitos da radiação , Camundongos , Células Mieloides/efeitos da radiação , Neutrófilos/efeitos da radiação , Papio , Fenilpropionatos/farmacologia , Exposição à Radiação/efeitos adversos , Taxa de Sobrevida , Irradiação Corporal Total/mortalidade
4.
J Infect Dis ; 209(12): 1929-40, 2014 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-24436452

RESUMO

No vaccines are available for human use for any parasitic infections, including the helminthic disease schistosomiasis. Sm-p80, the large subunit of Schistosoma mansoni calpain, is a leading antigen candidate for a schistosomiasis vaccine. Prophylactic and antifecundity efficacies of Sm-p80 have been tested using a variety of vaccine approaches in both rodent and nonhuman primate models. However, the therapeutic efficacy of a Sm-p80-based vaccine had not been determined. In this study, we evaluated the therapeutic efficacy of Sm-p80 by using 2 different strategies and 3 Sm-p80-based vaccine formulations in baboons. Vaccine formulations were able to decrease established adult worms by 10%-36%, reduce retention of eggs in tissues by 10%-57%, and decrease egg excretion in feces by 13%-33%, compared with control formulations. Marked differences were observed in B and T cell immune correlates between vaccinated and control animals. This is the first report of killing of established adult schistosome worms by a vaccine. In addition to distinct prophylactic efficacy of Sm-p80, this study adds to the evidence that Sm-p80 is a potentially important antigen with both substantial prophylactic and therapeutic efficacies. These data reinforce that Sm-p80 should be moved forward along the path toward human clinical trials.


Assuntos
Antígenos de Helmintos/imunologia , Calpaína/imunologia , Papio/parasitologia , Esquistossomose mansoni/tratamento farmacológico , Vacinas/imunologia , Animais , Anticorpos Anti-Helmínticos/sangue , Anticorpos Anti-Helmínticos/imunologia , Linfócitos B/imunologia , Modelos Animais de Doenças , Fezes/parasitologia , Feminino , Interferon gama/sangue , Interleucina-17/sangue , Interleucina-4/sangue , Leucócitos Mononucleares/imunologia , Masculino , Contagem de Ovos de Parasitas , Schistosoma mansoni/efeitos dos fármacos , Linfócitos T/imunologia , Vacinação
5.
Xenotransplantation ; 21(3): 287-90, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24547993

RESUMO

Baboons have natural antibodies against pig antigens. We have investigated whether there are differences in anti-non-Gal pig antibody levels between baboons maintained under specific pathogen-free (SPF) conditions and those housed under conventional conditions (non-SPF) that might be associated with improved outcome after pig-to-baboon organ transplantation. Baboons (n = 40) were housed indoors (SPF n = 8) or in indoor/outdoor pens (non-SPF n = 32) in colonies of similar size and structure. Non-SPF colonies harbor a number of pathogens common to non-human primate species, whereas many of these pathogens have been eliminated from the SPF colony. Complete blood cell counts (CBC), blood chemistry, and anti-non-Gal IgM and IgG levels were monitored. There were no significant differences in CBC or blood chemistry between SPF and non-SPF baboons. Anti-non-Gal IgM levels were significantly lower in the SPF baboons than in the non-SPF baboons (MFI 7.1 vs. 8.8, P < 0.05). One SPF and two non-SPF baboons had an MFI >20; if these three baboons are omitted, the mean MFIs were 4.8 (SPF) vs. 7.5 (non-SPF) (P < 0.05). Anti-non-Gal IgG was minimal in both groups (MFI 1.0 vs. 1.0). As their levels of anti-non-Gal IgM are lower, baboons maintained under SPF conditions may be beneficial for xenotransplantation studies as the initial binding of anti-pig IgM to an α1,3-galactosyltransferase gene-knockout pig organ may be less, thus resulting in less complement and/or endothelial cell activation. However, even under identical SPF conditions, an occasional baboon will express a high level of anti-non-Gal IgM, the reason for which remains uncertain.


Assuntos
Anticorpos Heterófilos/metabolismo , Modelos Animais , Papio , Organismos Livres de Patógenos Específicos , Suínos , Transplante Heterólogo , Animais , Biomarcadores/metabolismo , Feminino , Imunoglobulina G/metabolismo , Imunoglobulina M/metabolismo , Masculino , Papio/imunologia , Papio/metabolismo , Papio/cirurgia , Suínos/imunologia , Suínos/cirurgia
6.
Parasitol Res ; 113(6): 2239-50, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24728521

RESUMO

Based on data obtained using vaccine efficacy studies in mice, hamsters, and baboons, the credentials of Sm-p80 as a first tier vaccine candidate for schistosomiasis have been well established. Sm-p80-based vaccine formulation(s) have consistently exhibited potent prophylactic efficacy in reducing adult worm burden following cercarial challenge and induce killing of established adult worms in chronic infection. This vaccine is protective against both intestinal and urinary schistosomiasis. In this study, the longevity of Sm-p80-specific antibody responses was studied in mice and in baboons. Robust antibody titers were detected in mice for up to 60 weeks following vaccination with Sm-p80 recombinant vaccine (Sm-p80 + GLA-SE). In the follow-up experiments to our published studies, Sm-p80-specific IgG was also detected in baboons 5-8 years following the initial vaccination with an Sm-p80 DNA vaccine. In one baboon, transfer of Sm-p80-specific antibody was detected in umbilical cord blood and in the baby. These long-lasting humoral immune response data coupled with the vaccine efficacy data in rodents and nonhuman primates further strengthens the case for Sm-p80 to be moved forward through development leading to human clinical trials.


Assuntos
Anticorpos Anti-Helmínticos/sangue , Schistosoma mansoni/imunologia , Esquistossomose mansoni/prevenção & controle , Vacinas/imunologia , Animais , Antígenos de Helmintos/imunologia , Biomphalaria/parasitologia , Cricetinae , Feminino , Sangue Fetal/química , Sangue Fetal/imunologia , Imunidade Materno-Adquirida , Imunoglobulina G/sangue , Camundongos , Papio , Gravidez , Schistosoma mansoni/genética , Vacinação , Vacinas de DNA/imunologia
7.
Am J Primatol ; 75(8): 798-806, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23440922

RESUMO

Baboons (Papio hamadryas anubis) of a conventional breeding colony were nursery-reared to create a specific pathogen-free (SPF) baboon-breeding program. Because the founding generations were nursery-reared until 2 years of age, it was suspected that the SPF baboons would exhibit increased reproductive challenges as adults. Mothering behavior was of interest, because SPF females were not exposed to parental role models during the nursery-rearing process. We compared reproductive data from the SPF baboon breeding program during its first 10 years with data from age-matched baboons during the same period from an established, genetically-similar conventional breeding colony. We also evaluated records documenting mother-infant behaviors within the SPF colony. The average age of menarche in SPF females was 3.3 years. The overall live birth rate of both SPF and conventional females was approximately 90%, with no difference in pregnancy outcome between the two colonies. The average age at first conception for SPF females was earlier (4.2 years) than that of the conventional females (4.7 years). In both colonies, primiparous females were more likely to abort than multiparous females. Similarly, primiparous females were more likely to lose their infants to death or human intervention. A mothering score system was developed in the SPF colony to facilitate intervention of poor mother-infant relationships. Records revealed 70% of SPF mothers were able to raise one or more of their infants successfully to at least 180 days of age, which did not differ from conventional mothers. SPF females returned to post-partum amenorrhea 27 days sooner on average than the conventional females, independent of dam age. The nursery-rearing process used for recruitment into the SPF colony therefore did not have an adverse effect on reproduction or rearing offspring.


Assuntos
Criação de Animais Domésticos/métodos , Animais de Laboratório/psicologia , Papio/fisiologia , Reprodução/fisiologia , Aborto Animal , Animais , Feminino , Gravidez , Comportamento Social , Organismos Livres de Patógenos Específicos
8.
Ecology ; 93(4): 913-20, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22690641

RESUMO

Development and use of multistate mark-recapture models, which provide estimates of parameters of Markov processes in the face of imperfect detection, have become common over the last 20 years. Recently, estimating parameters of hidden Markov models, where the state of an individual can be uncertain even when it is detected, has received attention. Previous work has shown that ignoring state uncertainty biases estimates of survival and state transition probabilities, thereby reducing the power to detect effects. Efforts to adjust for state uncertainty have included special cases and a general framework for a single sample per period of interest. We provide a flexible framework for adjusting for state uncertainty in multistate models, while utilizing multiple sampling occasions per period of interest to increase precision and remove parameter redundancy. These models also produce direct estimates of state structure for each primary period, even for the case where there is just one sampling occasion. We apply our model to expected-value data, and to data from a study of Florida manatees, to provide examples of the improvement in precision due to secondary capture occasions. We have also implemented these models in program MARK. This general framework could also be used by practitioners to consider constrained models of particular interest, or to model the relationship between within-primary-period parameters (e.g., state structure) and between-primary-period parameters (e.g., state transition probabilities).


Assuntos
Sistemas de Identificação Animal , Cadeias de Markov , Modelos Biológicos , Trichechus manatus/fisiologia , Animais , Ecossistema , Dinâmica Populacional , Incerteza
9.
J Med Primatol ; 41(6): 341-8, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22905903

RESUMO

INTRODUCTION: Highly seasonal animals demonstrate predictable changes in immune function that coincide with changes in photoperiod. Little is known about the effect of season on immune response in baboons. The objective of this study was to determine the effect of season on inflammatory response in baboons. MATERIALS AND METHODS: Peripheral blood mononuclear cell cytokine response following immune stimulation and serum markers of inflammation were assessed during each season in two groups of young male baboons: one housed under natural light and one in a controlled environment of 12 hours light:12 hours dark. RESULTS: A seasonal immune rhythm was evident in both groups, with a greater TNF-α and IL-6 response to stimulation and serum CRP concentration in June and September compared with December. CONCLUSIONS: Season is an important experimental confounder, and therefore, time of year should be controlled when designing studies and analyzing data from immune studies in baboons.


Assuntos
Inflamação/veterinária , Doenças dos Macacos/imunologia , Papio/imunologia , Estações do Ano , Animais , Proteína C-Reativa/análise , Inflamação/imunologia , Interleucina-6/sangue , Leucócitos Mononucleares/imunologia , Masculino , Fotoperíodo , Fator de Necrose Tumoral alfa/sangue
10.
J Infect Dis ; 204(9): 1437-49, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21921206

RESUMO

The prophylactic efficacy of a schistosome antigen (Sm-p80) was tested in a nonhuman primate model, the baboon. Using a total of 28 baboons, different vaccination strategies were used including recombinant Sm-p80 protein formulated in Toll-like receptor 7 and Toll-like receptor 9 agonists, and DNA priming followed by boosting with protein plus adjuvants. Recombinant protein approaches provided levels of prophylactic efficacy of 52%-58%, whereas prime-boost approaches conferred 38%-47% protection in baboons. An appropriately balanced pro-inflammatory (T-helper 17 [Th17] and Th1) and anti-inflammatory (Th2) type of response was generated; the Th1 and Th17 types of immune responses appear to be indicative of increased prophylactic efficacy. Production and expression of several cytokines (interleukin 2 [IL-2], interferon γ, IL-12α, IL-1ß, IL-6, and IL-22) were up-regulated in vaccinated animals. Human correlate studies revealed Sm-p80 reactivity with immunoglobulin G in human serum samples from schistosome-infected individuals. In addition, a complete lack of prevailing Sm-p80-specific immunoglobulin E in a high-risk or infected population was observed, thus minimizing the risk of hypersensitivity reaction following vaccination with Sm-p80 in humans. This study provided the proof of concept to move Sm-p80 forward into further preclinical development leading to human clinical trials.


Assuntos
Anticorpos Anti-Helmínticos/sangue , Antígenos de Helmintos/imunologia , Doenças Endêmicas , Schistosoma mansoni/imunologia , Esquistossomose mansoni/imunologia , Esquistossomose mansoni/prevenção & controle , Vacinas de DNA/imunologia , Animais , Antígenos de Helmintos/administração & dosagem , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Imunoglobulina E/sangue , Imunoglobulina G/sangue , Masculino , Papio , Doenças dos Primatas/imunologia , Doenças dos Primatas/prevenção & controle , Soro/imunologia , Vacinação/métodos , Vacinas de DNA/administração & dosagem , Vacinas de Subunidades Antigênicas/administração & dosagem , Vacinas de Subunidades Antigênicas/imunologia
11.
Blood Cells Mol Dis ; 47(2): 107-16, 2011 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-21641240

RESUMO

The ß-hemoglobinopathies and thalassemias are serious genetic blood disorders affecting the ß-globin chain of hemoglobin A (α(2)ß(Α)(2)). Their clinical severity can be reduced by enhancing expression of fetal hemoglobin (γ-globin), producing HbF (α(2)γ(2,)). In studies reported here, γ-globin induction by 23 novel, structurally-unrelated compounds, which had been predicted through molecular modeling and in silico screening of a 13,000 chemical library, was evaluated in vitro in erythroid progenitors cultured from normal subjects and ß-thalassemia patients, and in vivo in transgenic mice or anemic baboons. Four predicted candidates were found to have high potency, with 4- to 8-fold induction of HbF. Two of these compounds have pharmacokinetic profiles favorable for clinical application. These studies thus effectively identified high potency γ-globin inducing candidate therapeutics and validated the utility of in silico molecular modeling.


Assuntos
Anemia/tratamento farmacológico , Produtos Biológicos/administração & dosagem , Desenho de Fármacos , Células Precursoras Eritroides/efeitos dos fármacos , Hemoglobina Fetal/biossíntese , Bibliotecas de Moléculas Pequenas/administração & dosagem , Talassemia beta/tratamento farmacológico , gama-Globinas/biossíntese , Administração Oral , Anemia/genética , Anemia/metabolismo , Animais , Produtos Biológicos/química , Produtos Biológicos/uso terapêutico , Células Cultivadas , Células Precursoras Eritroides/citologia , Células Precursoras Eritroides/metabolismo , Hemoglobina Fetal/genética , Expressão Gênica , Humanos , Injeções Intravenosas , Camundongos , Camundongos Transgênicos , Modelos Moleculares , Papio , Flebotomia , Reação em Cadeia da Polimerase , RNA Mensageiro/análise , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/uso terapêutico , Globinas beta/deficiência , Globinas beta/genética , Talassemia beta/genética , Talassemia beta/metabolismo , gama-Globinas/genética
12.
J Infect Dis ; 201(7): 1105-12, 2010 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-20187746

RESUMO

To date, no vaccine is available to prevent human schistosomiasis. We have targeted a protein of Schistosoma mansoni that plays an important role in the surface membrane renewal process, a mechanism widely believed to be utilized by the parasite as an immune evasion strategy. Sm-p80 antigen is a promising vaccine target because of its documented immunogenicity, protective efficacy, and antifecundity effects observed in both experimental murine and nonhuman primate models of this infectious disease. In the present study, we report that, in a vector approved for human use (VR1020), an Sm-p80-based DNA vaccine formulation confers a 46% reduction in the worm burden in a baboon (Papio anubis) model. Baboons vaccinated with Sm-p80-VR1020 had a 28% decrease in egg production after challenge with the infectious parasite. Sm-p80-VR1020 vaccine elicited robust immune responses to specific antigen Sm-p80, including immunoglobulin (Ig) G, its subtypes IgG1 and IgG2, and IgA and IgM in vaccinated animals. When stimulated in vitro with recombinant Sm-p80, peripheral blood mononuclear cells and splenocytes from baboons vaccinated with Sm-p80-VR1020 produced considerably higher levels of T helper 1 response-enhancing cytokines (interleukin [IL]-2 and interferon-gamma) than T helper 2 (Th2) response-enhancing cytokines (IL-4 and IL-10). Peripheral blood mononuclear cells produced a significantly higher number of spot-forming units for interferon-gamma than for IL-4 in enzyme-linked immunosorbent spot assays. A mixed T helper 1/T helper 2 type of humoral and T cell responses was generated after immunization with Sm-p80-VR1020. These findings again highlight the potential of Sm-p80 as a promising vaccine candidate for schistosomiasis.


Assuntos
Antígenos de Helmintos/imunologia , Papio/imunologia , Schistosoma mansoni/imunologia , Esquistossomose mansoni/prevenção & controle , Vacinas de DNA/imunologia , Animais , Anticorpos Anti-Helmínticos/sangue , Antígenos de Helmintos/genética , Células CHO , Células COS , Proliferação de Células , Chlorocebus aethiops , Cricetinae , Cricetulus , Ensaio de Imunoadsorção Enzimática , Proteínas de Helminto/genética , Proteínas de Helminto/imunologia , Imunoglobulina G/sangue , Interleucina-4/metabolismo , Intestinos/parasitologia , Leucócitos Mononucleares/metabolismo , Fígado/parasitologia , Contagem de Ovos de Parasitas , Schistosoma mansoni/genética , Esquistossomose mansoni/imunologia , Linfócitos T/imunologia , Vacinas de DNA/administração & dosagem
13.
Comp Med ; 71(2): 177-187, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33579397

RESUMO

Aging of the immune system is characterized by the loss of naïve T-cells, increased inflammation, and immune function impairment. Chronic infection with cytomegalovirus is thought to play a role in age-related changes in immunity. Therefore, to assess the effect of pathogens such as cytomegalovirus on the immune system, we determined lymphocyte populations and inflammatory markers over a 3-y period in captive, middle-age baboons, with various exposure to pathogens and shedding pressure. Groups included SPF (i.e., pathogen-negative; n = 14); large-group, conventionally housed (CONV LG; pathogen- positive; n = 14), and small-group, conventionally housed (CONV SM; pathogen-positive; n = 7). All baboon groups showed a decrease in CD45RA+ CD28+ (i.e., naive) cells over time during middle age, but the rate of decline appeared faster in CONV LG baboons than in the other groups. In addition, the reduction in CD45RA+ CD28+ cells in the CONV LG baboons coincided with higher IgG levels against baboon cytomegalovirus, increased serum cortisol concentration, and a greater inflammatory phenotype. The results of this project support a role for cytomegalovirus infection in immune system alterations in middle-aged baboons.


Assuntos
Infecções por Citomegalovirus , Papio anubis , Envelhecimento , Animais , Papio , Linfócitos T
14.
PLoS Pathog ; 4(9): e1000145, 2008 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-18773116

RESUMO

The peroxide response transcriptional regulator, PerR, is thought to contribute to virulence of group A Streptococcus (GAS); however, the specific mechanism through which it enhances adaptation for survival in the human host remains unknown. Here, we identify a critical role of PerR-regulated gene expression in GAS phagocytosis resistance and in virulence during pharyngeal infection. Deletion of perR in M-type 3 strain 003Sm was associated with reduced resistance to phagocytic killing in human blood and by murine macrophages in vitro. The increased phagocytic killing of the perR mutant was abrogated in the presence of the general oxidative burst inhibitor diphenyleneiodonium chloride (DPI), a result that suggests PerR-dependent gene expression counteracts the phagocyte oxidative burst. Moreover, an isogenic perR mutant was severely attenuated in a baboon model of GAS pharyngitis. In competitive infection experiments, the perR mutant was cleared from two animals at 24 h and from four of five animals by day 14, in sharp contrast to wild-type bacteria that persisted in the same five animals for 28 to 42 d. GAS genomic microarrays were used to compare wild-type and perR mutant transcriptomes in order to characterize the PerR regulon of GAS. These studies identified 42 PerR-dependent loci, the majority of which had not been previously recognized. Surprisingly, a large proportion of these loci are involved in sugar utilization and transport, in addition to oxidative stress adaptive responses and virulence. This finding suggests a novel role for PerR in mediating sugar uptake and utilization that, together with phagocytic killing resistance, may contribute to GAS fitness in the infected host. We conclude that PerR controls expression of a diverse regulon that enhances GAS resistance to phagocytic killing and allows adaptation for survival in the pharynx.


Assuntos
Proteínas de Bactérias/fisiologia , Viabilidade Microbiana , Proteínas Repressoras/fisiologia , Streptococcus pyogenes/patogenicidade , Fatores de Transcrição/fisiologia , Metabolismo dos Carboidratos/genética , Perfilação da Expressão Gênica , Humanos , Viabilidade Microbiana/genética , Estresse Oxidativo/genética , Faringe , Streptococcus pyogenes/genética , Virulência/genética
15.
J Am Vet Med Assoc ; 237(12): 1459-64, 2010 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-21155687

RESUMO

OBJECTIVE: To determine whether sublingual detomidine gel administration to horses would be effective in providing an appropriate degree of sedation and restraint to facilitate completion of veterinary and husbandry procedures under field conditions. DESIGN: Multicenter, prospective, randomized, blinded, placebo-controlled clinical study. ANIMALS: 270 client-owned horses known to require sedation or strong restraint to enable veterinary and husbandry procedures to be performed. PROCEDURES: Horses randomly received a single dose of detomidine gel (0.04 mg/kg [0.018 mg/lb]) or placebo gel administered sublingually. Horses were sedated to facilitate cleaning the prepuce, cutting of hair with electric clippers, hoof trimming or application of shoes, manual dental floating (ie, rasping or filing of the teeth to remove irregularities), nasogastric passage of a stomach tube or endoscope, and radiography. The primary determinant of efficacy was an assessment by a veterinarian on the ability or inability to successfully conduct the procedure. RESULTS: 171 horses met all the study protocol criteria. One hundred twenty-nine horses were treated with detomidine. The procedure was completed successfully for 76% (98/129) of the detomidine-treated horses, while the procedure was completed successfully for only 7% (3/42) of the placebo-treated horses. The percentage of horses in which the procedure was successfully completed was significantly different between detomidine-treated horses and placebo-treated horses. No serious adverse effects were reported. CONCLUSIONS AND CLINICAL RELEVANCE: Detomidine gel administered to horses sublingually at a dose of 0.04 mg/kg provided an appropriate degree of sedation and restraint to facilitate completion of veterinary and husbandry procedures in horses known to require sedation for such procedures.


Assuntos
Hipnóticos e Sedativos/uso terapêutico , Imidazóis/uso terapêutico , Administração Sublingual , Animais , Sedação Consciente/veterinária , Feminino , Hipnóticos e Sedativos/administração & dosagem , Imidazóis/administração & dosagem , Masculino
16.
Int J Pediatr Otorhinolaryngol ; 138: 110368, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33152962

RESUMO

OBJECTIVE: To evaluate which factors may affect anxiety and child's health perception of parents with children that have laryngomalacia. STUDY DESIGN: Survey Study. SETTING: "Coping with Laryngomalacia" - largest online laryngomalacia support group for parents with children who have laryngomalacia. SUBJECTS: and Methods: A survey was sent to support group member that gathered information regarding the patient's diagnosis and associated course of treatment and evaluated for parental anxiety and perceived health of their child. Analysis was performed to evaluate which variables are associated with increased parental anxiety and worsened perceived child's health. RESULTS: Data was gathered on 434 patients. All caregivers reported some level of anxiety due to the diagnosis and 64% felt completely anxious. Parents who saw an increased number of physicians prior to a pediatric ENT rated their child with poorer health (p < .05). Those that felt their concerns were brushed off initially reported increased anxiety (p < .05). If the child was admitted to the hospital, ICU, required intubation, had feeding troubles, required a feeding tube, or underwent pH monitoring, the patient was rated to have poorer health per the parents (p < .05). CONCLUSION: Laryngomalacia causes a significant burden on patients and their families due to the eating problems, feeding problems, hospital stay, and other various conditions associated with the disease. Caregivers should take a more modern and compassionate approach to management and diagnosis.


Assuntos
Cuidadores/psicologia , Efeitos Psicossociais da Doença , Laringomalácia , Grupos de Autoajuda , Ansiedade , Criança , Humanos , Laringomalácia/diagnóstico , Laringomalácia/terapia , Pais , Inquéritos e Questionários
17.
Ecology ; 90(2): 313-20, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19323213

RESUMO

The robust design has become popular among animal ecologists as a means for estimating population abundance and related demographic parameters with mark-recapture data. However, two drawbacks of traditional mark-recapture are financial cost and repeated disturbance to animals. Mark-resight methodology may in many circumstances be a less expensive and less invasive alternative to mark-recapture, but the models developed to date for these data have overwhelmingly concentrated only on the estimation of abundance. Here we introduce a mark-resight model analogous to that used in mark-recapture for the simultaneous estimation of abundance, apparent survival, and transition probabilities between observable and unobservable states. The model may be implemented using standard statistical computing software, but it has also been incorporated into the freeware package Program MARK. We illustrate the use of our model with mainland New Zealand Robin (Petroica australis) data collected to ascertain whether this methodology may be a reliable alternative for monitoring endangered populations of a closely related species inhabiting the Chatham Islands. We found this method to be a viable alternative to traditional mark-recapture when cost or disturbance to species is of particular concern in long-term population monitoring programs.


Assuntos
Passeriformes/fisiologia , Projetos de Pesquisa , Animais , Dinâmica Populacional , Ratos
18.
Biometrics ; 65(1): 237-46, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18479484

RESUMO

Although mark-resight methods can often be a less expensive and less invasive means for estimating abundance in long-term population monitoring programs, two major limitations of the estimators are that they typically require sampling without replacement and/or the number of marked individuals available for resighting to be known exactly. These requirements can often be difficult to achieve. Here we address these limitations by introducing the Poisson log and zero-truncated Poisson log-normal mixed effects models (PNE and ZPNE, respectively). The generalized framework of the models allow the efficient use of covariates in modeling resighting rate and individual heterogeneity parameters, information-theoretic model selection and multimodel inference, and the incorporation of individually unidentified marks. Both models may be implemented using standard statistical computing software, but they have also been added to the mark-recapture freeware package Program MARK. We demonstrate the use and advantages of (Z)PNE using black-tailed prairie dog data recently collected in Colorado. We also investigate the expected relative performance of the models in simulation experiments. Compared to other available estimators, we generally found (Z)PNE to be more precise with little or no loss in confidence interval coverage. With the recent introduction of the logit-normal mixed effects model and (Z)PNE, a more flexible and efficient framework for mark-resight abundance estimation is now available for the sampling conditions most commonly encountered in these studies.


Assuntos
Ecossistema , Densidade Demográfica , Software/normas , Animais , Colorado , Simulação por Computador , Distribuição de Poisson , Dinâmica Populacional , Sciuridae
19.
BMC Med Educ ; 9: 29, 2009 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-19500392

RESUMO

BACKGROUND: Indiana University School of Medicine (IUSM) employs eight regional basic science campuses, where half of the students complete their first two years of medical school. The other half complete all four years at the main campus in Indianapolis. The authors tested the hypothesis that training at regional campuses influences IUSM students to pursue primary care careers near the regional campuses they attended. METHODS: Medical school records for 2,487 graduates (classes of 1988-1997) were matched to the 2003 American Medical Association Physician Masterfile to identify the medical specialty and practice location of each graduate. Multivariate logistic regression was performed to assess the effect of regional campus attendance on students' choice of medical specialty and practice location, while simultaneously adjusting for several covariates thought to affect these career outcomes. RESULTS: Compared to Indianapolis students, those who attended a regional campus were somewhat more likely to be white, have parents with middle class occupations, and score slightly lower on the Medical College Admission Test. Any such differences were adjusted for in the regression models, which predicted that four of the regional campuses were significantly more likely than Indianapolis to produce family practitioners, and that five of the regional campuses were significantly more likely than the others to have former students practicing in the region. When analyzed collectively, attendance at any regional campus was a significant predictor of a primary care practice located outside the Indianapolis metropolitan area. CONCLUSION: Attending a regional campus for preclinical training appears to increase the likelihood of practicing primary care medicine in local communities.


Assuntos
Comportamento de Escolha , Medicina , Área de Atuação Profissional/tendências , Faculdades de Medicina , Especialização , Estudantes de Medicina/psicologia , Adulto , Estudos de Coortes , Feminino , Humanos , Indiana , Modelos Logísticos , Masculino
20.
Comp Med ; 69(1): 55-62, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30704552

RESUMO

Cytomegalovirus (CMV) is a common chronic herpesvirus found in humans and numerous other mammalian species. In people, chronic viruses like CMV can alter overall health and immunity and pose a serious risk for those with an inadequate immune system. In addition, CMV plays an important role in animal health, and could affect the health of vulnerable populations, like endangered species. Previous studies found a high rate of CMV seropositivity among adult baboons (Papio anubis), and results from our laboratory revealed that baboon CMV (BaCMV) seropositivity was correlated with altered immune cell populations. In the current study, we further characterized BaCMV infection in normal, adult baboons. Analysis of blood samples from baboons (age, 6 to 26 y) revealed a low overall prevalence of detectable of BaCMV DNA, with a higher detection rate in aged baboons (older than 15 y). Furthermore, data suggest that individual baboons maintain similar rates of recurrence and levels of BaCMV shedding in saliva over time. Finally, we evaluated multiple commercially available assays for antihuman CMV IgG and IgM for use with baboon sera. Results of this study will improve our understanding of BaCMV and may be directly relevant to other closely related species.


Assuntos
Infecções por Citomegalovirus/veterinária , Doenças dos Macacos/patologia , Papio anubis , Fatores Etários , Animais , Anticorpos Antivirais/sangue , Infecções por Citomegalovirus/sangue , Infecções por Citomegalovirus/imunologia , Infecções por Citomegalovirus/patologia , DNA Viral/sangue , Doenças dos Macacos/sangue , Doenças dos Macacos/imunologia , Saliva/virologia , Eliminação de Partículas Virais
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